Pregnancy Bump
Portrait of a woman in a striped dress holding her pregnancy bump.

Results from a mouse study carried out at the University of Maryland School of Medicine suggest that an unhealthy vaginal microbiome could increase the likelihood of infant mortality and have an adverse effect on how babies develop.

However, as described in the journal Nature Communications, the research team thinks that the impact of an unhealthy vaginal microbiome could be lessened by changes in lifestyle factors such as consuming a healthy diet with high levels of fruits and vegetables during pregnancy.

When babies are born their first exposure to micro-organisms is normally from their mother’s vaginal microbiome during their journey through the birth canal. The composition of the microbes varies considerably in different women and, of course, babies born by caesarean section have a different first exposure to microbes.

“Newborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood,” write the authors.

Research has suggested that exposure to an abnormal vaginal microbiome, typically characterized by the presence of too many species of microbes, could have a negative impact on infant health. Research has shown five distinct microbiome groupings in humans, with four being healthy and one unhealthy (Community state type (CST) IV).

“CST I, II, III, and V are dominated by the presence of Lactobacillus species and represent the most common communities in the cervicovaginal space. An additional vaginal community state type, CST IV, is defined by an absence of Lactobacillus and the presence of anaerobic bacteria, including Snethia, Prevotella, Megasphaera, Gardnerella vaginalis, and Atopobium vaginae,” explain the authors.

Women with chronic diseases such as diabetes, cardiovascular disease or who are obese are known to be at higher risk of having an unhealthy vaginal microbiome. Women from low-income neighborhoods with limited access to healthcare and good nutrition are also at higher risk.

“We know what is healthy for mom is healthy for baby’s brain development, and on the flip side stress contributes to disease risk” said Tracy Bale, Professor of Pharmacology at the University of Maryland School of Medicine, who led the study, in a press statement. “We wanted to identify biological factors that predict these negative health outcomes and determine how each one contributes to these inequities in our society.”

Previous work by Bale and team using the same mouse model showed that pups born by C-section who were exposed to vaginal microbiomes from stressed mothers had different outcomes to those exposed to microbiomes from unstressed mothers. They showed differences in brain development and how they responded to stress later in life

In this study, the researchers carried out more in-depth investigation into why these differences were present between the two groups of infant mice. Female mice were inoculated with either a healthy or unhealthy human vaginal microbiome. Pups born to these mothers via C-section were then exposed to the same microbiomes to simulate the kind of exposure they would have if born through a vaginal birth. As before, differences were seen between the two groups of pups.

“CST IV males showed a significant increase in body weight. We further observed shifts in circulating immune composition and changes to gene expression patterns in the paraventricular nucleus of the hypothalamus in CST IV adult males, which may reflect altered feeding patterns and metabolic regulation that could manifest in changes to growth trajectories and body weight observe postnatally,” write the researchers.

The team also assessed the impact of nutrition by carrying out a second study where some female mice were given an unhealthy high fat, low fiber diet versus their normal low fat, high fiber diet.

Strikingly, 60% of the pups born to mice with an unhealthy vaginal microbiome who also ate an unhealthy diet died 48 hours after birth. This figure halved if the mice with the unhealthy vaginal microbiome ate a healthy diet.

“The vaginal microbiome component led to dramatic changes in the brain through fetal immune system development, and it appears that this overactive immune system seems to up the risk for infant mortality,” said Bale.

“In humans we had observed these associations with unhealthy vaginal microbiomes, but now our work is allowing us to make these connections and to identify the mechanisms that ultimately affect pregnancy outcomes, perhaps as novel biomarkers that could be used in identifying women at risk.”

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